Associations between HLA and autoimmune neurological diseases with autoantibodies

Abstract

Recently, several autoimmune neurological diseases have been defined by the presence of autoantibodies against different antigens of the nervous system. These autoantibodies have been demonstrated to be specific and useful biomarkers, and most of them are also pathogenic. These aspects have increased the value of autoantibodies in neurological practice, as they enable to establish more accurate diagnosis and to better understand the underlying mechanisms of the autoimmune neurological diseases when they are compared to those lacking them. Nevertheless, the exact mechanisms leading to the autoimmune response are still obscure. Genetic predisposition is likely to play a role in autoimmunity, HLA being the most reported genetic factor. Herein, we review the current knowledge about associations between HLA and autoimmune neurological diseases with autoantibodies. We report the main alleles and haplotypes, and discuss the clinical and pathogenic implications of these findings.

HLA and immunological features of SARS-CoV-2-induced Guillain-Barré syndrome

“…The class II allele DRB1*03:01 was also associated with GBS in Iraq [10], while DQB1*05:01 was linked with severe GBS in a study performed in Germany [11]. Further studies are needed to conclude on the relevance of these findings, but it is likely that HLA plays a role in this setting as in other autoimmune neurological syndromes [12], including those triggered by infections.…”

Autoimmune encephalitis and gastrointestinal dysmotility: achalasia, gastroparesis, and slow transit constipation

“…AA involved in autoimmune encephalitis are classified as group I antibodies (e. g., an-tiHU, antiCV2, antiglutamic acid decarboxylase, anti-Ma/Ta, antiglutamic acid decarboxylase) targeting intracellular neuronal antigens, are more closely associated with an underlying malignancy, and use the same cytotoxic T-cell mechanisms when targeting the intracellular neuronal antigens and onconeuronal antigens as part of the immune response to cancer [3][4][5][6]. Group II antibodies (N-methyl D-aspartate receptor, voltage-gated potassium channel, voltage-gated calcium channel, gamma-aminobutyric acid receptor, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) target cell surface neuronal antigens, are less likely to be associated with an underlying malignancy, and use more "restricted" humoral immune mechanisms of neurotoxicity that typically respond better to early immunomodulatory therapy [3][4][5][6]. In addition, typical NAD with gastrointestinal manifestation include the area postrema syndrome in neuromyelitis optica, the dipeptidyl-peptidase-like protein 6-associated encephalitis, and the autoimmune autonomic and enteric neuropathies [2,4,7].…”

“…In addition, typical NAD with gastrointestinal manifestation include the area postrema syndrome in neuromyelitis optica, the dipeptidyl-peptidase-like protein 6-associated encephalitis, and the autoimmune autonomic and enteric neuropathies [2,4,7]. Among these AA, ANNA-1 targeting intracellular neuronal antigens as part of the immune response is most frequently seen in paraneoplastic syndromes [3][4][5][6]. For example, ANNA-1 is associated in more than 95 % with small cell lung cancer [8] and SOX-1 in small cell lung cancer and Hodgkin disease [9].…”

“…AA-triggered gastrointestinal dysmotility [3][4][5][6][7] does not follow a specific pattern. Therefore, the type of gastrointestinal motility disturbances does not necessarily point to NAD.…”

“…For example, antibodies targeting chemoreceptors (such as the area postrema) or enteric neurons may result in severe vomiting, early satiety, dysphagia, or diarrhea [2]. The autoantibodies (AA) in autoimmune encephalitis affect not only CNS structures but also gastrointestinal functions [3][4][5][6][7]. Among these, limbic encephalitis is the most consistent finding, representing a spectrum of immune-mediated diseases involving various regions of the central nervous system such as the neocortex, striatum, hindbrain, spine, and peripheral nervous system [3][4][5][6].…”